Specific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to the allergenicity of vaccines. Allergenicity is conferred by the presence of intact B-cell epitopes that crosslink allergen-specific IgE on effector cells. The use of linear peptide sequences representing fragments of the native allergen is one approach to reduce allergenicity. Preclinical models of peptide immunotherapy have demonstrated efficacy in both autoimmunity and allergy. Translation of this technology into the clinic has gained momentum in recent years based on encouraging results from early clinical trials. To date, efforts have focused on two major allergens, but vaccines to a broader range of molecules are currently in clinical development. Mechanistically, peptide immunotherapy appears to work through the induction of adaptive, allergen-specific regulatory T cells that secrete the immunoregulatory cytokine IL-10. There is also evidence that peptide immunotherapy targeting allergen-specific T cells can indirectly modulate allergen-specific B-cell responses. Peptide immunotherapy may provide a safe and efficacious alternative to conventional subcutaneous and/or sublingual approaches using native allergen preparations.